Mechanisms of drug response and resistance in Giardia duodenalis

Abstract

Giardia duodenalis is a parasitic protist and the most common intestinal parasite of humans, causing 200-300 million cases of diarrhoeal disease annually. Metronidazole is a widely administered anti-giardial drug, but treatment failure is relatively common, attributed in part to metronidazole resistance in the infecting parasites. This drug enters parasitic cells as a pro- drug, which is activated to cytotoxic intermediate forms via oxidoreductase enzymes in the parasite’s antioxidant system. Metronidazole-resistant lines — defined here as those that exhibit significantly greater tolerance to the drug in vitro compared to wild-type cells, show perturbed transcription and activity of various ..